Myosin complexed with ADP and blebbistatin reversibly adopts a conformation resembling the start point of the working stroke

Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6799-804. doi: 10.1073/pnas.0907585107. Epub 2010 Mar 29.

Abstract

The powerstroke of the myosin motor is the basis of cell division and bodily movement, but has eluded empirical description due to the short lifetime and low abundance of intermediates during force generation. To gain insight into this process, we used well-established single-tryptophan and pyrene fluorescent sensors and electron microscopy to characterize the structural and kinetic properties of myosin complexed with ADP and blebbistatin, a widely used inhibitor. We found that blebbistatin does not weaken the tight actin binding of myosin.ADP, but unexpectedly it induces lever priming, a process for which the gamma-phosphate of ATP (or its analog) had been thought necessary. The results indicate that a significant fraction of the myosin.ADP.blebbistatin complex populates a previously inaccessible conformation of myosin resembling the start of the powerstroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry*
  • Adenosine Triphosphate / chemistry
  • Animals
  • Binding Sites
  • Dictyostelium / metabolism*
  • Fluorescent Dyes / chemistry
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Kinetics
  • Microscopy, Electron / methods
  • Microscopy, Fluorescence / methods
  • Models, Biological
  • Molecular Conformation
  • Myosins / chemistry*
  • Protein Conformation
  • Rabbits

Substances

  • Fluorescent Dyes
  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Myosins